The hypothalamus and limbic system are known to play a critical role in the mediation of central effects on the endocrine system and on the autonomic innervation of the viscera, as well as in the mediation of related behavioral responses that assure homeostasis of energy and water balance, and of body temperature. The long-range goal of our research is to clarify the organization and neurotransmitter specificity of the neural circuitry underlying these responses. During the last 10 years we have taken advantage of powerful new neuroanatomical methods, based on the axonal transport of specific markers and on immunohistochemistry, to re-examine many of the connections of the limbic system and hypothalamus in the rat. The results have led us to consider in detail the organization of cell groups and pathways that could mediate the integration of endocrine and autonomic responses, and we have focussed on the connections of the paraventricular nucleus of the hypothalamus (PVH), which we have shown to contain 3 separate groups of cells that project to the posterior pituitary, median eminence and autonomic cell groups. Interestingly, we have also shown that 3 noradrenergic cell groups in the brainstem, which receive vagal sensory information, project to different parts of the PVH, and appear to coordinate the integration of endocrine and autonomic responses. The proposed work is a direct continuation of these neuroanatomical studies, and is based on the use of anterograde transport, multiple retrograde transport, and combined rerograde transport-immunohistochemical methods. Specifically, we propose to do the following. I. To test the hypothesis that the PVH contains a fourth functionally distinct subdivision that projects to limbic structures including the septum, amygdala, prefrontal cortex and habenula. If this is true, we shall go on to determine which of 8 possible neurotransmitters are contained within these pathways. 2. To determine the origin of forebrain inputs to the PVH, and to discribe the distribution of each in relation to the 8 cytoarchitectonically-defined subdivisions of the nucleus. 3. To determine the organization of projections from the medial preoptic area, which is thought to play a critical role in the mediation of blood pressure, ingestive behavior, sexual behavior, and thermoregulation. And 4, to determine whether the lateral preoptic area gives rise to pathways that may be involved in the coordination of visceral and somatomotor responses. This work is designed to clarify the organization of basic neural mechanisms involved in the central regulation of the cardiovascular system, adrenal gland, and pancreas, and of ingestive behavior. The results may have important implications for the study of mechanisms underlying essential hypertension, diabetes, and obesity.